Effect of Intravitreal Aflibercept vs Laser Photocoagulation on Treatment Success of Retinopathy of Prematurity
Authors: Andreas Stahl, Emine A. Sukgen, Wei-Chi Wu, Domenico Lepore, Hidehiko Nakanishi, Jan Mazela, Darius M. Moshfeghi, Robert Vitti, Aditya Athanikar, Karen Chu, Pablo Iveli, Fei Zhao, Thomas Schmelter, Sergio Leal, Evra Köfüncü, Noriyuki Azuma, Pablo Larrea, Matthias Bolz, Patricia Delbeke, Nilva de Moraes, Maria Regina Bentlin, Violeta Chernodrinska, Christina Grupcheva, Liliyana Dimitrova, Vasil Marinov, Magdalena Kovacova, Juraj Timkovic, Ioannis Asproudis, Agathi Kouri, Asimina Mataftsi, Wai Ching Lam, Erzsebet Princzkel, Hana Leiba, Luca Buzzonetti, Carlo Cagini, Domenico Lepore, Silvia Gabriella Osnaghi, Mitsuru Arima, Hideyuki Hayashi, Tomoka Kambe, Mariko Kiyota, Hiroyuki Kondo, Shunji Kusaka, Tomoko Miyazato, Eiichiro Noda, Yuta Saito, Yasunobu Saneyoshi, Tetsuju Sekiryu, Takako Tachikawa, Nor Akmal Bahari, Stefan de Geus, Jan Mazela, Ana Almeida, Susana Teixeira, Narcis Berlea, Delia Nicoara, Vladimir Brzheskiy, Yulia Gorelik, Eyvgeny Sidorenko, Irina Trifanenkova, Gavin Tan, Dana Tomcikova, Sang Jin Kim, So Young Kim, Joo Yong Lee, Jesús Peralta Calvo, Julia Escudero Gómez, Pilar Tejada Palacios, Ann Hellström, Yu-Hung Lai, Hsiang-Ling Tsai, Imren Vardarli Akkoyun, Hikmet Basmak, Sibel Caliskan Kadayifcilar, Muhammet Erol, Sengul Ozdek, Emine Sukgen, Sally Painter, Mykola Aryayev
Journal: JAMA (2022)

Laser photocoagulation, which is the standard treatment for retinopathy of prematurity (ROP), can have adverse events. Studies of anti-vascular endothelial growth factor injections have suggested efficacy in the treatment of ROP, but few studies have directly compared them with laser treatments.To compare intravitreal aflibercept vs laser photocoagulation in infants with ROP requiring treatment.This noninferiority, phase 3, 24-week, randomized clinical trial was conducted in 27 countries (64 hospital sites) throughout Asia, Europe, and South America. Overall, 118 infants (gestational age ≤32 weeks at birth or birth weight ≤1500 g) with ROP severity (zone I stage 1+ [stage 1 plus increased disease activity], zone I stage 2+, zone I stage 3, zone I stage 3+, zone II stage 2+, or zone II stage 3+) requiring treatment or with aggressive posterior ROP in at least 1 eye were enrolled between September 25, 2019, and August 28, 2020 (the last visit occurred on February 12, 2021).Infants were randomized 2:1 to receive a 0.4-mg dose of intravitreal aflibercept (n = 75) or laser photocoagulation (n = 43) at baseline. Additional treatment was allowed as prespecified.The primary outcome was the proportion of infants without active ROP and unfavorable structural outcomes 24 weeks after starting treatment (assessed by investigators). The requirement for rescue treatment was considered treatment failure. Intravitreal aflibercept was deemed noninferior if the lower limit of the 1-sided 95% bayesian credible interval for the treatment difference was greater than -5%.Among 118 infants randomized, 113 were treated (mean gestational age, 26.3 [SD, 1.9] weeks; 53 [46.9%] were female; 16.8% had aggressive posterior ROP, 19.5% had zone I ROP, and 63.7% had zone II ROP) and 104 completed the study. Treatment (intravitreal aflibercept: n = 75; laser photocoagulation: n = 38) was mostly bilateral (92.9%), and 82.2% of eyes in the intravitreal aflibercept group received 1 injection per eye. Treatment success was 85.5% with intravitreal aflibercept vs 82.1% with laser photocoagulation (between-group difference, 3.4% [1-sided 95% credible interval, -8.0% to ∞]). Rescue treatment was required in 4.8% (95% CI, 1.9% to 9.6%) of eyes in the intravitreal aflibercept group vs 11.1% (95% CI, 4.9% to 20.7%) of eyes in the laser photocoagulation group. The serious adverse event rates were 13.3% (ocular) and 24.0% (systemic) in the intravitreal aflibercept group compared with 7.9% and 36.8%, respectively, in the laser photocoagulation group. Three deaths, which occurred 4 to 9 weeks after intravitreal aflibercept treatment, were considered unrelated to aflibercept by the investigators.Among infants with ROP, intravitreal aflibercept compared with laser photocoagulation did not meet criteria for noninferiority with respect to the primary outcome of the proportion of infants achieving treatment success at week 24. Further data would be required for more definitive conclusions regarding the comparative effects of intravitreal aflibercept and laser photocoagulation in this population.ClinicalTrials.gov Identifier: NCT04004208.